Through this application M. D. Anderson Cancer Center seeks funding for a new Prostate Cancer SPORE. Under the leadership of Dr. Christopher J. Logothetis, Principal Investigator, and Dr. Timothy C. Thompson, Co-Principal Investigator, who are recognized internationally for their research in prostate cancer, the M. D. Anderson Cancer Center Prostate SPORE has created a stable and dynamic infrastructure for translational research that works toward the development of non-morbid therapies for patients with localized prostate cancer; the identification of predictive biomarkers for therapeutic response; the development of new biologically targeted therapeutic agents; and the linkage of epidemiological and molecular signaling profiles for virulent prostate cancer. We continue to build on our capacity to conduct novel and innovative clinical trials and believe that new research projects conducted by our translational research team will yield substantial progress and meaningful changes in clinical practice. In the current proposal we define our translational research objectives as (1) development of quantitative tools for determination of aggressive prostate cancers; (2) testing of novel therapeutic agents in proof of principle clinical trials; (3) development of predictive biomarkers for identification of patients who will respond to targeted therapies; and (4) development of rational strategies for combination therapies. We will achieve these translational research objectives by identifying and testing obesity-related biomarkers for virulent prostate cancer, clinical testing of GLIPR1-ATM protein and a novel ligand-directed pro-apoptotic peptide (BMTP-11) for prostate cancer, and conducting two hypothesis-driven clinical trials with a novel FGF signaling inhibitor (TKl 258), and combination Src inhibitor (Dasatinib)+Docetaxel in patients with advanced prostate cancer. We will accomplish our goals through 5 research projects (including one population science research project), 3 support cores (Administrative, Biostatistics and Bioinformatics, and Specimen), a dynamic Developmental Research Program and an effective Career Development Program. We are optimistic that our research efforts will contribute to reductions in the incidence of, and morbidity and mortality from, this devastating disease by translating basic research into clinical practice.